1. Field of the Invention
The invention relates to implantable medical devices, one example of which is a stent. More particularly, the invention relates to a method of coating such implantable medical devices.
2. Description of the Background
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to remodel the vessel wall. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.
A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings, which can collapse and occlude the conduit after the balloon is deflated. Vasospasms and recoil of the vessel wall also threaten vessel closure. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may necessitate another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis a stent is implanted in the lumen to maintain the vascular patency.
Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the opening wall of the passageway. Typically, stents are capable of being compressed so that they can be inserted through small lumens using catheters and then expanded to a larger diameter once they are at the desired location. Mechanical intervention using stents has reduced the rate of restenosis as compared to balloon angioplasty. Yet, restenosis is still a significant clinical problem with rates ranging from 20-40%. When restenosis does occur in the stented segment, its treatment can be challenging, as clinical options are more limited as compared to lesions that were treated solely with a balloon.
Stents are used not only for mechanical intervention, but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or even toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results.
One proposed method of medicating stents involves using a polymeric carrier coated onto the stent surface. A composition including a solvent, a dissolved polymer, and a dispersed active agent is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent surfaces a coating of the polymer and the active agent impregnated in the polymer.
A potential shortcoming of the foregoing method of medicating stents is that the active agent release rate may be too high to provide an effective treatment. This shortcoming may be especially pronounced with certain active agents. For instance, it has been found that the release rate of 40-O-(2-hydroxy)ethyl-rapamycin from a standard polymeric coating can be greater than 50% in about 24 hours in certain release media. Thus, there is a need for a coating that reduces active agent release rates in order to provide a more effective release-rate profile.
Another shortcoming of the foregoing method of medicating stents is that there can be significant manufacturing inconsistencies. For instance, there can be release rate variability among different stents. There are many ways to change drug release rate. The most frequent used methodology is to vary drug-to-polymer ratio. When a slower or faster release is preferred in a certain drug eluting stent application, there is a need to have a manufacturing method to achieve it without the change of drug-polymer formulation.
When some polymers dry on a stent surface to form a coating, different polymer morphologies may develop for different stent coatings, even if the coating process parameters appear to be consistent. The differences in polymer morphology may cause the active agent release rate to vary significantly. These inconsistencies may cause clinical complications. Additionally, when stents are stored, the coating can change and exhibit “release rate drift.” In other words, two substantially similar stents may exhibit different release rates based predominantly on the time the stents were stored. Yet another source of release rate variability is caused by the coating, during the coating process, drying at different rates.
Thus, there is a need for a method that reduces the stent-to-stent release rate variability among stents and over time. The rate of drying, or solvent removal, from the coating can affect the distribution of drug within the coating. The present invention provides a method and coating to meet the foregoing as well as other needs.